Synthesis and Cytotoxicity Evaluation of N-(5-(Substituted-benzylthio)-1,3,4-thiadiazole-2-yl)-2-p-nitrophenylacetamide Derivatives as Potential Anticancer Agents

Abstract

<em>Cancer is a big global problem and is one of the top and main causes of mortality in developed countries. Many of the current treatments and anticancer therapeutics have problems with severe side effects and on the other hand, the drug resistance is also another obstacle in the cancer chemotherapy. Hence, there is a strong demand for the discovery and development of effective new antineoplastic therapies. According to the in vitro effectiveness of 1,3,4-thiadiazole based compounds as anticancer agents, new 1,3,4-thiadiazole based derivatives with various electron withdrawing and electron donating moieties were synthesized and tested by MTT assay against three cancerous cell lines. PC3 (Prostate cancer), U87-C-531 (Glioblastoma) and MDA-MB-231 (Breast cancer) cell lines were applied for MTT assay and obtained results were compared to imatinib. Study of the structure activity relationship of prepared compounds showed electron withdrawing substituents such as Cl, F and NO₂ enhanced the anticancer properties compared </em><em>to compound without any substituent (compound 3l) or compounds with electron donating (methoxy)</em><em> substituent (compounds 3j and 3k). Totally, compound 3a (IC₅₀ = 10.6 µM) showed superior activity against PC3 cell line and compounds 3d (IC₅₀ = 10.3 µM), 3h (IC₅₀ = 12.5 µM) and 3j (IC₅₀ = 11.3 µM) exhibited higher activity against MDA-MB-231 cell line compared to imatinib as reference drug.</em>